Effect of cholecystokinin on cytokines during endotoxic shock in rats

AIM To study the effect of cholecystokinin-octapeptide (CCK-8) on systemic hypotension and cytokine production in lipopolysaccharide (LPS)-induced end otoxic shock (ES) rats. METHODS The changes of blood pressure were observed using physiological rec ord instrument in four groups of rats: LPS (8 mg . kg(-1), iv) induced ES; CCK-8 (40 mug . kg(-1), iv) pretreatment 10 min before LIPS (8 mg.kg(-1)), CCK-8 (40 mug.kg(-1), iv) or normal saline (control) groups Differences in tissue and circulating specificity of the proinflammatory cytokines (TNF-al pha, IL-1 beta and IL-6) were assayed with ELISA kits. RESULTS CCK-8 reversed LPS-induced decrease of mean artery blood pressure ( MABP) in rats. Compared with control, LPS elevated the serum level of IL-6 significantly (3567 + 687 ng.L-1 vs 128 +/- 22 ng.L-1, P <0.01), while cont ents of TNF-a and IL-1P elevated significantly (277 +/- 86 ng.L-1 vs not de tectable and 43 +/- 9 ng.L-1 vs not detectable, P<0.01) but less extent tha n IL-6. CCK-8 significantly inhibited the LPS-induced increase in serum TNF -<alpha>, IL-1 beta and IL-6. LPS elevated spleen and lung content of IL-1P significantly (5184 +/- 85 ng.L-1 vs 1047 +/- 21 ng.L-1 and 4050 +/- 614 n g.L-1 vs not detectable, P<0.01), while levels of TNF-a and IL-6 also rose significantly but in less extent than IL-1<beta>. CCK-8 inhibited the LPS-i nduced increase of the cytokines in spleen and lung. In the heart, CCK-8 si gnificantly inhibited LPS-induced increase of TNF-alpha (864 +/- 123 ng.L-1 in CCK-8 + LPS group vs 1599 +/- 227 ng.L-1 in LPS group, P <0.01), and IL -1 beta (282 +/- 93 ng.L-1 in CCK-8 + LPS group vs 621 +/- 145 ng.L-1 in LI PS group, P <0.01). CONCLUSION CCK-8 reverses ES, which may be related to its inhibitory effect on the overproduction of cytokines.